Serum Magnesium Measurements After Parathyroidectomy for Primary Hyperparathyroidism: Should It be Routine?

Background

Parathyroidectomy is the treatment of choice in primary hyperparathyroidism (PHPT). Following surgery, significant changes in bone and mineral metabolism may follow, but routine magnesium monitoring is not standard practice. The occurrence of significant clinical events linked to hypomagnesaemia in 3 patients after parathyroidectomy led to our evaluation of magnesium levels after surgery for PHPT.

Methods

Serum magnesium levels before and after parathyroidectomy for PHPT were prospectively evaluated in a single centre over a year. The incidence and severity of hypomagnesaemia and its correlation with other biochemical variables were assessed.

Results

A total of 138 patients underwent parathyroidectomy for PHPT. Pre-operative and day 1 post-operative serum magnesium levels were available in 57/138 (41.3%) and 99/138 (71.7%) patients, respectively. Serum magnesium decreased significantly after surgery (mean ± SD of 0.85 ± 0.08 and 0.75 ± 0.11 mmol/L, respectively, p < 0.001). On the day after parathyroidectomy, 31/99 (31.3%) patients had hypomagnesaemia (<0.70 mmol/L); in 3 of whom it was severe (<0.50 mmol/L). Patients with hypomagnesaemia had lower pre-operative magnesium (mean ± SD of 0.78 ± 0.06 and 0.87 ± 0.07 mmol/L, p < 0.001), higher pre-operative calcium [median (IQR) of 2.83 (2.71–2.99) and 2.71 (2.63–2.80) mmol/L, p = 0.001] and higher post-operative calcium [median (IQR) of 2.41 (2.30–2.51) and 2.35 (2.28–2.43) mmol/L, p = 0.046] compared to those with normomagnesaemia. In addition, these patients demonstrated higher drop in calcium levels after surgery (0.44 ± 0.20 and 0.35 ± 0.18 mmol/L, p = 0.033). Magnesium levels after surgery correlated positively with pre-operative magnesium (r = 0.561, p < 0.001) and post-operative PTH (r = 0.210, p = 0.037) and negatively with pre-operative adjusted calcium (r = − 0.389, p < 0.001).

Conclusions

Serum magnesium decreased significantly following parathyroidectomy for PHPT and nearly a third of patients developed post-operative, mostly mild hypomagnesaemia. Whilst routine serum magnesium measurements could facilitate prompt recognition and treatment of this electrolyte disturbance, further research needs to establish the clinical importance of mild hypomagnesaemia in these clinical settings and, if indicated, to devise optimal treatment strategies.

     

Serum,urinary and stone zinc,iron, magnesium and copper levels in idiopathic calcium oxalate stone patients

Many theories have been put forward to explain the mechanism of stone formation and growth. The aim of this study was to investigate the urinary, serum and stone levels of zinc, iron, magnesium, and copper in patients with calcium oxalate stones and to investigate urinary and serum element levels in healthy controls and to find a possible connection between the elements and calcium oxalate stone formation. A total of 104 patients with calcium oxalate stones ranging in age from 3 to 79 years (mean 44.0 ± 18.1) and 77 healthy controls ranging in age from 18 to 77 (mean 44.2 ± 17.9) were included in this study. The mean urinary iron and copper levels in stone patients were significantly higher than healthy controls (P = 0.000). The mean urinary zinc and magnesium levels in healthy controls were significantly higher than stone patients (P = 0.000). There was no significant difference in the serum levels of magnesium and copper in stone patients and healthy controls. Serum zinc and iron level were significantly high in healthy controls as compared to stone patients. Each stone had all 4 elements. Zn and Mg have inhibitory effect on calcium oxalate stone formation. Fe and Cu could be promotor of the calcium oxalate stone formation.     

Diagnostic problems associated with cystinuria

To elucidate the role of the urinary cystine concentration for the formation of urinary stones, 190 stone-formers were evaluated in this prospective study. Seven patients (3.8%) were heterozygous and one patient (0.5%) was homozygous for cystinuria; only two (1%) of them were cystine stone-formers. Two patients with calcium stones were heterozygous for cystinuria. This study confirms the observation that elevated concentrations of urine cystine are relatively infrequent among patients with urinary stones.     

Studies of urinary risk factors in urolithiasis

Urinary excretions of calcium, oxalate and uric acid were estimated in 160 stone-formers (male 118, female 42) and 257 healthy controls (male 207, female 50). Stone-formers were divided into two groups according to their stone analysis: calcium containing stone-formers and non-calcium stone-formers. Calcium stone-formers were divided again into those who had a single stone episode and multiple or recurrent stone episodes. Urinary calcium and oxalate showed significant increases in calcium stone-formers, while urinary uric acid increased only in male calcium stone-formers. Recurrent calcium stone-formers demonstrated significant high levels of urinary calcium excretion especially in males, whereas no difference of urinary oxalate excretion between recurrent and single stone-formers. The frequency distributions on the excretion of three subjects were estimated respectively in patients with calcium stone and in controls. Relative risks, risk curves and stone probabilities were proposed and compared. The higher excretion values of urinary calcium and oxalate closely related to higher risks of forming calcium stones. On the other hand, urinary uric acid did not have such a relation to calcium stone formation. We defined the states which urinary excretions exceeded 95% upper confidence limits of normal controls as hyperexcretions. Hypercalciuria was more than 200 mg/day in male and female, hyperoxaluria was 50 mg/day in male and 45 mg/day in female and hyperuricosuria was 850 mg/day in male and 650 mg/day in female according to our definition. Among male calcium stone-formers, hypercalciuria was found in 45.3%, hyperoxaluria in 26.4% and hyperuricosuria in 15.1%. While in female calcium stone-formers, hypercalciuria in 23.7%, hyperoxaluria in 26.3% and hyperuricosuria in 13.2%. Of the male calcium stone-formers 57.5% showed either or both hypercalciuria and hyperoxaluria, and recurrent stone-formers also demonstrated a higher incidence among them. Excretion products of urinary calcium and oxalate were calculated and compared in each group. Calcium stone-formers showed significant high values especially in male recurrent stone-formers. The estimation by combining some risk factors will provide more useful means of assessing severity of urinary calculous diseases and therapeutic effects of their various treatments.     

Role of the urinary calcium in the growth of calcium stone

We analyzed the relationship between the rate and clinical factors. The growth rate per year of the stone was measured by Nabeshima's method in 29 male patients with renal calcium stones including 7 pure calcium oxalate (CaOx) stones and 22 mixed calcium oxalate and calcium phosphate (CaOx-CaP) stones. The 24-hour urinary excretion of calcium, phosphate, uric acid and magnesium were assayed under an ambulatory free diet in 5 patients with CaOx stones and 15 with CaOx-CaP stones. The relationship between the growth rate and the urinary excretion of stone-forming parameters was examined. We found a significant positive correlation between the growth rate of calcium stones and the urinary excretion of calcium (p<0.02). In addition, the growth rate of CaOx-CaP stone was significantly higher than that of pure CaOx stone (p<0.05). In conclusion, urinary calcium is important for the growth of renal calcium stones.     

Relationship between metabolic acidosis and calcium phosphate urinary stone formation in women

The relationship between the degree of metabolic acidosis and calcium phosphate stone formation was studied. Furthermore, the reasons why renal tubular acidosis (RTA) and primary hyperparathyroidism (PHPT) dominantly occur in women, and female stone formers more often produce calcium phosphate stone are discussed. Blood was slightly more acidotic in women than in men in both the urolithiasis and the control groups. Likewise, blood was significantly more acidotic and urinary pH significantly higher in patients with PHPT. Patients with RTA had severe metabolic acidosis, and urinary pH was highest among all groups. Calcium phosphate concentration was significantly higher in women than in men, and was also higher in patients with PHPT than in those with urolithiasis. All patients with RTA had pure calcium phosphate stones. The reasons why females are more acidotic and have more calcium phosphate in stones are suspected to be related to progesterone and urinary tract infection.     

Sporadic and MEN1‐Related Primary Hyperparathyroidism: Differences in Clinical Expression and Severity

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ～2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1‐related versus sporadic PHPT (sPHPT). We performed a 36‐mo cross‐sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1‐related PHPT. Serum calcium, phosphate, PTH, 25(OH)D₃, and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z‐scores at the LS (?1.33 ± 1.23 versus ?0.74 ± 1.4, p = 0.008) and FN (?1.13 ± 0.96 versus ?0.6 ± 1.07, p = 0.002) and lower phosphate (2.38 ± 0.52 versus 2.56 ± 0.45 mg/dl, p = 0.003) and PTH (113.8 ± 69.5 versus 173.7 ± 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07–8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28–2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62–50.00; p = 0.0001). In conclusion, MEN1‐related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.     

An assessment of parathyroid hormone,calcitonin, 1,25 (OH)<Subscript>2</Subscript> vitamin D3, estradiol and testosterone in men with active calcium stone disease and evaluation of its biochemical risk factors

The aim of this study is to investigate the serum levels of parathyroid hormone (PTH), calcitonin, 1,25 (OH)₂ vitamin D3, estradiol and testosterone in male patients with active renal calcium stone disease compared with controls and investigate their relationship with serum/urinary biochemistry. Male active renal calcium stone formers (ASF) were enrolled from December 2008 to April 2009. Controls were selected from age and sex matched individuals. Two 24-h urine samples and a blood sample were withdrawn from each participant while they were on free diet. Serum 1,25 (OH)₂ vitamin D3 levels in the ASF and control groups were 127 ± 40 and 93 ± 35 pmol/l (p < 0.001). Serum levels of PTH, calcitonin, estradiol and testosterone were not statistically different between the ASF and control groups (all p > 0.05). Serum 1,25 (OH)₂ vitamin D3 was associated with higher urinary excretion of calcium and phosphorus in ASF patients. Serum levels of calcitonin were related to less urinary excretion of calcium in the control group. Serum testosterone was related to higher urinary excretion of uric acid in ASF patients and to higher urinary excretion of oxalate in the control group. 1,25 (OH)₂ Vitamin D3 is an important hormone in the pathogenesis of recurrent renal calcium stone disease and could increase renal stone risk by increasing the urinary excretion of calcium and phosphorus. There is a possibility of testosterone involvement in the pathogenesis of renal stones through higher urinary uric acid and oxalate excretion.     

The value of the 24-hour urine analysis in the assessment of stone-formers attending a general hospital outpatient clinic

The daily urinary excretion of calcium, oxalate, uric acid and glycosaminoglycans, and 24-h urinary volume and pH, were measured in 39 normal men and 65 male patients who had formed at least one calcium oxalate stone. No significant difference could be found between the two groups of subjects with respect to any of the urinary parameters. Nonetheless, a higher proportion of stone-formers than normals had daily excretion levels of oxalate in excess of the normal 95th percentile. On the other hand, there was no difference between the proportion of stone-formers and normals who fell into this category with respect to calcium excretion. It was concluded that a single 24-h urine analysis is of limited practical value in explaining the occurrence of stones or in predicting the likelihood of further episodes in unselected stone-formers attending a general hospital outpatient clinic.     

Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease

Oxalate excretion was measured in healthy subjects and idiopathic calcium stone-formers on dietary regimens which differed in the type and amount of protein allowed; 24-h urine collections were obtained from 41 practising vegetarians and 40 normal persons on a free, mixed, "mediterranean" diet. Twenty idiopathic calcium stone-formers were also studied while on two low calcium, low oxalate diets which differed in that animal protein was high in one and restricted in the other. Vegetarians had higher urinary oxalate levels than controls and although the calcium levels were markedly lower, urinary saturation with calcium/oxalate was significantly higher. This mild hypercalciuria was interpreted as being secondary to both a higher intake and increased fractional intestinal absorption of oxalate. Changing calcium stone-formers from a high to a low animal protein intake produced a significant decrease in calcium excretion but there was no variation in urinary oxalate. As a result, the decrease in calcium oxalate saturation was only marginal and not significant. It was concluded that dietary animal protein has a minimal effect on oxalate excretion. Mild hyperoxaluria of idiopathic calcium stone disease is likely to be intestinal in origin. Calcium stone-formers should be advised to avoid an excess of animal protein but the risks of a vegetable-rich diet should also be borne in mind.     

Calcium stone disease: a multiform reality

In calcium renal stones, calcium oxalate and calcium phosphate in various crystal forms and states of hydration can be identified. Calcium oxalate monohydrate (COM) or whewellite and calcium oxalate dihydrate (COD) or weddellite are the commonest constituents of calcium stones. Calcium oxalate stones may be pure or mixed, usually with calcium phosphate or sometimes with uric acid or ammonium urate. The aim of this study was to compare the clinical and urinary patterns of patients forming calcium stones of different composition according to infrared spectroscopic analysis in order to obtain an insight into their etiology. The stones of 84 consecutive calcium renal stone formers were examined by infrared spectroscopy. In each patient, a blood sample was drawn and analysed for serum biochemistry and a 24-h urine sample was collected and analysed for calcium, phosphate, oxalate, citrate and other electrolytes. We classified 49 patients as calcium oxalate monohydrate (COM) stone formers, 32 as calcium oxalate dihydrate (COD) stone formers and three as apatite stone formers according to the main component of their stones. Patients with COM stones were significantly older than patients with COD stones (P<0.002). Mean daily urinary calcium and urinary saturation with respect to calcium oxalate were significantly lower in patients with COM than in those with COD stones (P<0.000). Patients with calcium oxalate stones containing a urate component (10%) presented with higher saturation (P<0.012) with respect to uric acid in their urine (and lower with respect to calcium oxalate and calcium phosphate, respectively P<0.024 and P<0.003) in comparison with patients without a urate component in the stone. Patients with calcium oxalate stones with a calcium phosphate component (15%) showed higher (P<0.0016) urinary saturation levels with respect to calcium phosphate (and lower with respect to uric acid (P<0.009), compared with patients forming stones without calcium phosphate or with a low calcium phosphate component. Patients with calcium stones mixed with urate had a significantly lower urinary pH (P<0.002) and urinary calcium (P<0.000), and patients with calcium phosphate >15%, higher urinary pH (P<0.004) and urinary calcium (P<0.000). In conclusion, in the evaluation of the individual stone patient, an accurate analysis of the stone showing its exact composition and the eventual presence of minor components of the stone is mandatory in order to plan the correct prophylactic treatment. Patients with calcium stones could require various approaches dependent on the form and hydration of the calcium crystals in their stones, and on the presence of minor crystalline components that could have acted as epitaxial factors.     

Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasties

Stones are a common complication of the storage of urine in intestinal reservoirs. Previous studies have identified predisposing physical characteristics in the reservoirs. Biochemical and dietary factors have been little investigated. Fifteen patients (6 males and 9 females) who had undergone various enterocystoplasty operations and who had subsequently formed either upper or lower urinary tract stones were investigated. The programme has been previously described and included stone, blood and urine analysis and dietary review. Comparison was made with 15 age- and sex-matched idiopathic stone formers with normal bladders. Stones were infective in origin in 86% of cases, and 14% were sterile. Metabolic screen showed that 80% of enterocystoplasty patients had risk factors for at least three different types of stone. All patients had raised pH (mean 6.93) and hypocitraturia. Five had a raised alkaline phosphatase. Raised serum and urinary calcium, hyperoxaluria and hyperuricosuria were found in 33% of patients. Five had a 24-h urine volume below 1.6 l/day. All patients had a high risk index (P _SF) for phosphatic stones and 12 also for calcium oxalate stones. Compared to age-and sex-matched idiopathic stone-formers, the urine had a higher pH, sodium and protein excretion and a lower calcium and citrate excretion. Although the patients were already selected as stone-formers, the data show that metabolic and dietary factors are present. They may be as important in the aetiology of the stones, as the already recognised factors of infection and poor reservoir drainage. Investigation should include such factors, the presence of which may be taken into account in a prophylactic regime.     

May an Altered Hypothalamo–Pituitary–Adrenal Axis Contribute to Cortical Bone Damage in Primary Hyperparathyroidism?

Cortisol secretion has been reported to be increased in primary hyperparathyroidism (PHPT). Our aim was to evaluate circulating and urinary cortisol levels and the relationships with biochemical and bone parameters in patients with PHPT at the time of diagnosis. We studied 180 consecutive patients with PHPT (mean age ± SD 60.0 ± 13.2 years; F/M 140/40, BMI 25.8 ± 4.8 kg/m²) and 56 subjects with incidentally discovered adrenal adenoma who served as controls (age 56.2 ± 12.8 years, F/M 40/16, BMI 25.7 ± 3.9 kg/m²). Serum morning and midnight cortisol and urinary free cortisol were measured in both groups. In PHPT patients bone mineral density was measured at the lumbar spine, femur, and forearm. Serum morning cortisol and urinary cortisol were similar in PHPT patients and controls, whereas midnight cortisol was higher in PHPT patients (5.3 ± 4.7 vs. 2.9 ± 0.9 μg/dL, P = 0.001). In this group, midnight cortisol correlated positively with age (r = 0.27, P = 0.008) and negatively with forearm (r = −0.36, P = 0.003) and total-femur T score (r = −0.30, P = 0.02). Multivariate regression analysis, including age, calcium, parathyroid hormone (PTH), and midnight cortisol as independent variables and forearm T score as dependent variable, indicated that age (β = –0.29, P < 0.0001), PTH (β = –0.33, P < 0.0001), and midnight cortisol (β = –0.14, P < 0.04) were independently associated with forearm T score. Our findings show increased midnight cortisol levels in patients with PHPT, indicating a subtle alteration of the hypothalamo–pituitary–adrenal axis dynamics that is unrelated to the degree of disease activity; further data are needed to demonstrate the supplementary effect of this subtle alteration to bone damage in this condition.     

N -Acetylneuraminic acids (nana): a potential key in renal calculogenesis

N-Acetylneuraminic acids (NANA) promote binding of calcium ions to macromolecules and cells, increase the intrinsic viscosity of glycoproteins and facilitate gel formation in water. Since these properties are crucial in urinary calculogenesis, we evaluated NANA levels in urine and serum as well as their expression in kidney tissues. Using a modified thiobarbituric acid assay, the evaluation of free and bound NANA in 24-h urine samples revealed a ratio of 1.87 in 33 non-stone-formers but a reversed ratio of 0.84 in 41 recurrent calcium oxalate stone-formers. Time kinetics revealed a gradual rise in NANA expression until 48 h of culture and a significantly higher release into supernatants of papillary renal epithelial cells (REC) when compared with cortical REC. To examine NANA distribution in kidney tissues, paraffin-embedded biopsies from five normal and six stone-forming kidneys were labeled with the biotinylated NANA-specific lectins Maackia amurensis (MAA) and Sambucus nigra (SNA). Immunohistochemistry revealed intense luminal MAA reactivity of distal tubular REC and collecting ducts in 96.7% and 91.5% of normal and stone-forming kidneys respectively. By contrast, there was a marked difference between normal and stone-forming kidneys for SNA reactivity (17.7% vs 95%) at the same locations. Finally, the glycocalyx of recurrent stone-formers showed altered sialylglycoside linkages [α(2,6) instead of α(2,3)] that may indicate an altered REC function. Given the calcium-binding potential of NANA, their increased local concentration within the glycocalyx layer in the distal nephron may either initiate stone formation or facilitate attachment of microcrystals to REC. Received: 14 November 1996 / Accepted: 17 June 1997     

Assessment of crystallization risk formulas in pediatric calcium stone-formers

The pathogenesis of calcium urolithiasis involves complex interactions of urinary promoters and inhibitors of crystallization. A variety of risk formulas have been established to approximate these interactions for clinical evaluation, and the aim of our study was to determine their usefulness as predictors of stone formation. The study cohort comprised 126 patients (63 boys and 63 girls) aged 6.7–18 years (mean age 14.1 ± 2.9 years) with calcium urolithiasis (61 with chemically confirmed calcium oxalate stones and 65 children with a strong clinical suspicion of this type of urolithiasis). Of these, 36 children were classified as recurrent stone-formers, whereas the remaining 90 had experienced only one stone episode. The values obtained were compared to those of a control group of 60 age- and gender- matched healthy children. A number of crystallization risk indices were calculated from analytes obtained in 24-h urine: calcium/magnesium ratio (Ca/Mg), calcium/citrate ratio (Ca/Cit), (calcium × oxalate)/(magnesium × citrate) ratio (CaOx/MgCit), relative urinary CaOx supersaturation (RS_CaOx), CaOx activity product index (AP_CaOx), and standardized CaOx activity product index (AP_{CaOx stand}). All indices, except for the AP_CaOx index, were significantly higher in stone-formers than in the controls. The Ca/Mg, Ca/Cit, CaOx/MgCit, AP_CaOx, and AP_{CaOx stand} indices were significantly higher in recurrent stone-formers than in first-episode ones. However, the determination of precise cutoffs between pathological and non-pathological values was problematic due to a considerable overlap of individual values. Based on our results, we conclude that calculation of the majority of risk indices may play a rather supplementary role in the evaluation of children with calcium urolithiasis.     

Effect of verapamil on urinary stone-forming risk factors

Prevention of recurrent stone formation will only be possible with careful metabolic evaluation and appropriate management. In this present prospective study, a total of 95 patients with calcium oxalate (CaOx) stone disease were evaluated with respect to the effects of a calcium channel blocking agent (verapamil) therapy on stone-forming risk factors. A total of 95 patients with CaOx urolithiasis were well evaluated for the possible specific effects of verapamil administration on stone-forming risk factors during long-term follow-up. All patients had calcium-containing stones with normal renal morphology and function without any urinary tract infection. The follow-up period ranged from 12 to 36.6 months, with a mean value of 24.4 months. The age of the patients (54 male and 41 female; M/F: 1.31) ranged from 20 to 46 years (mean 34.3 years). On metabolic evaluation all patients had some kind of risk factors and patients were independently randomized into two groups, namely group 1 (n = 49): patients receiving calcium entry blocker, verapamil hydrochloride (isoptin 240 mg KKH tablets, oral t.i.d.); group 2 (n = 46): patients receiving no specific therapy (control patients) that were matched for sex and age. Follow-up results (at least 1 year) with respect to the changes in urinary stone-forming risk factors were recorded in both groups. During long-term follow-up patients undergoing no specific therapy did not show a significant change with respect to the urinary levels of stone-forming risk factors when compared with the others receiving verapamil on a regular basis. In the light of our results as well as the literature data, we believe that the pathophysiological mechanisms underlying the effect of verapamil on stone formation (as a result of enhanced crystal deposition) and on the excretion of the urinary stone-forming risk factors have to be well evaluated in further experimental as well as clinical studies. Although the exact mechanism of action is not clear; we may claim that the limitation of internal calcium shift by these agents may also well effect the tubular process related to oxalate handling which ultimately limits its excretion in urine.     

Rapid Communication: relative effect of urinary calcium and oxalate on saturation of calcium oxalate

BACKGROUND: The study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate. METHODS: A retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A "theoretical" curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents. RESULTS: At the stability constant of 7.07 x 10(3), the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 x 10(3) from the Equil 2 that is considered the "gold standard," calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r= 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r= 0.73 unadjusted and 0.60 adjusted, P <0.0001 for oxalate). CONCLUSION: Among calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate.     

Calcium oxalate saturation in dialysis patients with and without primary hyperoxaluria

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9±16.5, 138.1±54.9 μmol/l, 2.30±0.28, and 1.07±0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9±34.3, 197.9±63.5 μmol/l, 2.53±0.15, and 1.14±0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1<SS<8.9), which was associated with a serum oxalate level of more than 30 μmol/l. Serum saturation exceeded the formation product (SS=8.9) in some specimens from patients with type 1 primary hyperoxaluria. The serum calcium oxalate saturation [SS(CaOx)] showed a significant positive correlation with the levels of oxalate [Ox], calcium [Ca], and citrate [Cit]: (all mmol/l, r=0.9848, P<0.01). This formula is useful for estimating the saturation. In conclusion, the serum oxalate level is a good indicator of calcium oxalate saturation and should be monitored accurately while keeping it lower in dialysis patients.     

Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria

Absorptive hypercalciuria (AH), a common stone-forming condition characterized biochemically by intestinal hyperabsorption of calcium and hypercalciuria may be associated with bone loss. In AH type I (AH-1), hypercalciuria persists despite restriction in dietary calcium intake. We therefore hypothesized that the skeleton may contribute to the hypercalciuria in this subgroup of patients. Histomorphometric analysis of iliac crest biopsies were performed on nine stone-formers with AH-1 and on nine matched normal subjects. After stabilization on a stone-prevention diet, calcium homeostasis in the stone formers was then evaluated on inpatient constant metabolic diet before and after short-term blockade of bone resorption by alendronate (10 mg daily, 17 days total). Compared with controls, the stone-formers had lower indices of bone formation (osteoblast surface/bone surface 1.8+/-2.1 vs 3.0+/-1.5%, P=0.04; wall thickness 35.8+/-6.9 vs 47.2+/-7.6%, P=0.001) and relatively higher bone resorption (osteoclast surface/bone surface 0.4+/-0.2 vs 0.2+/-0.2%, P=0.05). In the stone-formers, a short-term course of alendronate treatment corrected fasting urinary calcium (0.14+/-0.06 to 0.06+/-0.04 mg Ca/mg Cr, P=0.001) and marginally reduced 24-h urinary calcium by 48 mg/day (P=0.06). Increased intestinal calcium absorption and hypercalciuria persisted, but estimated calcium balance improved (P=0.007). Our results suggest that the hypercalciuria of AH-1 originates primarily from intestinal hyperabsorption of calcium, but bone resorption in excess of bone formation may contribute.     

Clinical and biochemical profile of patients with “pure” uric acid nephrolithiasis compared with “pure” calcium oxalate stone formers

The purpose of the present study was to compare the clinical characteristics of “pure” uric acid (UA) stone formers with that of “pure” calcium oxalate (CaOx) stone formers and to determine whether renal handling of UA, urinary pH, and urinary excretion of promoters and inhibitors of stone formation were different between the two groups. Study subjects comprised 59 patients identified by records of stone analysis: 30 of them had “pure” UA stones and 29 had “pure” CaOx nephrolithiasis. Both groups underwent full outpatient evaluation of stone risk analysis that included renal handling of UA and urinary pH. Compared to CaOx stone formers, UA stone formers were older (53.3 ± 11.8 years vs. 44.5 ± 10.0 years; P = 0.003); they had higher mean weight (88.6 ± 12.5 kg vs. 78.0 ± 11.0 kg; P = 0.001) and body mass index (29.5 ± 4.2 kg/m² vs. 26.3 ± 3.5 kg/m²; P = 0.002) with a greater proportion of obese subjects (43.3% vs. 16.1%; P = 0.01). Patients with “pure” UA lithiasis had significantly lower UA clearance, UA fractional excretion, and UA/creatinine ratio, with significantly higher serum UA. The mean urinary pH was significantly lower in UA stone formers compared to CaOx stone formers (5.17 ± 0.20 vs. 5.93 ± 0.42; P < 0.0001). Patients with CaOx stones were a decade younger, having higher 24-h urinary calcium excretion (218.5 ± 56.3 mg/24 h vs. 181.3 ± 57.1 mg/24 h; P = 0.01) and a higher activity product index for CaOx [AP (CaOx) index]. Overweight/obesity and older age associated with low urine pH were the principal characteristic of “pure” UA stone formers. Impairment in urate excretion associated with increased serum UA was also another characteristic of UA stone formers that resembles patients with primary gout. Patients with pure CaOx stones were younger; they had a low proportion of obese subjects, a higher urinary calcium excretion, and a higher AP index for CaOx.